Modeling Parkinson's disease falls associated with brainstem cholinergic systems decline

Behavioral Neuroscience
Aaron Kucinski, Martin Sarter

Abstract

In addition to the primary disease-defining symptoms, approximately half of patients with Parkinson's disease (PD) suffer from postural instability, impairments in gait control and a propensity for falls. Consistent with evidence from patients, we previously demonstrated that combined striatal dopamine (DA) and basal forebrain (BF) cholinergic cell loss causes falls in rats traversing dynamic surfaces. Because evidence suggests that degeneration of brainstem cholinergic neurons arising from the pedunculopontine nucleus (PPN) also contributes to impaired gait and falls, here we assessed the effects of selective cholinergic PPN lesions in combination with striatal DA loss or BF cholinergic cells loss as well as losses in all 3 regions. Results indicate that all combination losses that included the BF cholinergic system slowed traversal and increased slips and falls. However, the performance of rats with losses in all 3 regions (PPN, BF, and DA) was not more severely impaired than following combined BF cholinergic and striatal DA lesions. These results confirm the hypothesis that BF cholinergic-striatal disruption of attentional-motor interactions is a primary source of falls. Additional losses of PPN cholinergic neurons may worse...Continue Reading

Citations

Sep 21, 2016·The International Journal of Neuroscience·Kavelin RumallaManoj K Mittal
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Jan 25, 2017·Neuroscience and Biobehavioral Reviews·Qu TianStephanie A Studenski
Oct 27, 2017·Movement Disorders : Official Journal of the Movement Disorder Society·Alfonso FasanoLynn Rochester
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Mar 16, 2019·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Elisa PelosinLaura Avanzino
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Feb 18, 2016·NPJ Parkinson's Disease·Santiago Perez-Lloret, Francisco J Barrantes
Nov 27, 2020·Journal of Clinical Medicine·Sooyeoun YouHyung Lee
Jan 12, 2021·The European Journal of Neuroscience·Nicole E ChambersChristopher Bishop
Mar 19, 2021·Psychopharmacology·Aaron Kucinski, Martin Sarter

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